There is a known method for measuring the concentration (or activity) of a specific ion contained in a liquid (tap water, river water, sewage, industrial waste, water, etc.) and a biological body fluid (blood, urine, saliva, etc.) using an ion-selective electrode.
The methods for such measurement include wet-type method and dry-type method. Generally in the wet-type method, a barrel-type electrode having a reference liquid inside the electrode is used. However, this type of electrode is difficult in handling in maintenance, washing, conditioning, life, break and the like of the electrode, and has a defect that some hundred or more microliter of a sample liquid is required in order to dip an electrode in the sample liquid.
In order to eliminate such inconveniences, a method of using a dry-type, film-shaped, ion-selective electrode has been proposed. The dry-type ion-selective electrode is a measuring tool (also referred to as a tool for measuring ion activity) for potentiometrically measuring the concentration of a specific ion contained in a drop amount of an aqueous liquid, particularly a biological body fluid such as blood, urine and saliva. Its basic constitution has been described in Japanese Examined Patent Application Nos. 1991-54788 and 1992-50530 and the like. The ion-selective electrode is a dry-type electrode film having a basic constitution which comprises a support, a conductive metal layer (e.g., silver layer), a layer containing a water-insoluble salt of the metal (e.g., silver chloride layer), an electrolytic layer containing an electrolytic salt (e.g., potassium chloride and sodium chloride) which has the same anion as that of the water-insoluble salt and a cation (e.g. potassium ion and sodium ion) and a binder; and an ion-selective membrane, which are integrally laminated in this order. Two of the electrode films are made in a pair, connected with a bridging member, and connected to a potentiometer and then, the sample liquid (test liquid) and a standard liquid (reference liquid) are spotted on each electrode film, and an electric potential is measured. Thus, the concentration of a specific ion in the sample liquid can be determined. According to the dry-type method using the film-shaped ion-selective electrode, no maintenance is needed for the electrode, the measuring tool can be miniaturized and thus, the ion concentration can be measured on bedside and the amount of the sample liquid necessary for measurement can be largely reduced.
By changing the type of the ion-selective membrane of the dry-type ion-selective electrode, the concentration of inorganic ions such as hydrogen ion (H+), lithium ion (Li+), sodium ion (Na+), potassium ion (K+) magnesium ion (Mg2+) calcium ion (Ca2+), chlorine ion (Cl−), bicarbonate ion (HCO3−) or carbonate ion (CO32−), can be measured.
On the other hand, a complex ion-selective electrode has also been known wherein the ion concentrations of a plurality of ion species can be simultaneously measured by incorporating a plurality of ion-selective electrodes in a measuring tool and supplying a test liquid and a reference liquid once respectively. For example, such electrode is described in Japanese Examined Patent Application Nos. 1992-7657.7 and 1993-56819.
It is clinically important to measure concentrations of the above described inorganic ions in the biological body fluid. Among these inorganic ions, measurement of the concentration of ionized calcium (iCa) in blood is indispensable for diagnosis of calcium metabolic anomaly (e.g., accessory thyroid gland dysfunction, and bone metastasis of a cancer). It is an important measurement item in the monitoring of calcium supply in blood transfusion during a surgical operation (calcium ions may bind to citric acid which is added as an anticoagulant, and blood calcium ion may be reduced) and in the clinical examination screening. On the other hand, the hydrogen ion concentration (pH) is an index for knowing acid-base equilibrium of the body fluid and therefore is an important measurement item. Generally in such clinical examinations, an ionized calcium concentration in blood has been normalized for the concentration at pH 7.4. However, for the normalization, the calcium ion concentration as well as the hydrogen ion concentration must be measured together with.
The dry-type ion-selective electrode is a microchip constituted basically of simple structure as described above, and requires a very small amount of the sample liquid. Therefore, it is very useful in the case where the amount of the sample liquid is limited such as the body fluid. In addition, there are such advantages that the ion-selective electrode having such simple and micro structure can be handled independently from the potentiometer and can be replaced by a new electrode in every measurement.
So far, as ion-selective electrodes of dry-type and multilayered film-type, Na, K and Cl electrodes have already been marketed. The concentration of target ions for measurement in the reference liquid has been adjusted to be within an almost normal range in blood. A principle of measurement based on differential method is mentioned below. As represented by the following formula, one electrode of the pair of left and right electrodes is spotted with the standard liquid (reference liquid) having a known concentration, and the other electrode is spotted with the sample liquid, and differential electric potential occurred in both the electrodes is measured, and the concentration of the specific ion in the sample liquid is determined.Eref.=E0+(N/z)·Log(Aref.)Esample=E0+(N/z)·Log(Asample)E=Esample−Eref.=(N/z)·Log(Asample/Aref.)wherein,    E: differential electric potential    Aref.: ion activity in reference liquid    Eref.: electric potential of reference electrode    Asample: ion activity in sample liquid    Esample: electric potential of sample electrode    N: Nernst coefficient    E0: electric potential of standard electrode    z: ionic valence.
In the method based on this measuring principle, when a composition of the reference liquid is set to be similar to the concentration of target ions contained in the sample liquid, the electric potential occurred is small, which is preferable for electric potential measurement. Moreover, so-called junction potential occurring at a liquid junction is suppressed to enable measurement with good precision. Following this, the composition of the reference liquid of the pH electrode is set, to be a normal pH range in blood.
However, even by using the reference liquid prepared as described above, there remains such a problem that the electric potential shift (drift) is large in accordance with time period passed after start of measurement. When this drift phenomenon differs between electrodes, measured values may vary and a practical problem arises. Further, this phenomenon reduces in time sequence after production of the electrode. In other words, the electrode immediately after production differs from the electrode in a certain period after production in an electric potential response, and therefore a measurement using a specific calibration curve can not be carried out. Consequently, calibration operation must be carried out for every measurement occasion, but it is comlicated.